PROJECT SUMMARY/ABSTRACT Urinary tract infection (UTI) is the most common serious bacterial infection in childhood, affecting approximately 3% of all children by six years of age. The current standard of care for young children who present with UTI is to perform a voiding cystourethrogram (VCUG) to evaluate for the presence of vesicoureteral reflux (VUR), a condition found in approximately 30-40% of children with UTI that is thought to increase the risk of renal scarring and renal insufficiency. Children found to have VUR after a UTI are treated with daily prophylactic antibiotics until the VUR resolves, or have surgical correction of the VUR. In recent years, our understanding of the relationship of UTI, VUR, and renal scarring, and current strategies for managing children with UTI have been challenged. It is now clear that renal scarring can occur in children who do not have VUR, and that most children with even high grade VUR do not develop renal scarring, suggesting that factors other than VUR determine the development of renal scarring. In the fall of 2005, the NIDDK began funding RIVUR (Randomized Intervention for Vesicoureteral Reflux;U01-DK074064), a 5-year multicenter randomized controlled trial designed to evaluate the effectiveness and harms of prophylactic antimicrobials for the prevention of recurrent UTIs and renal scarring in children with an initial UTI and presence of VUR on a VCUG. Three of the clinical trial centers participating in RIVUR will be recruiting patients at the time of UTI diagnosis and will be screening them for presence of VUR. Rather than completely dismissing those who do not have VUR, we propose to enroll them in an ancillary observational study to understand more fully the factors that place a child at risk of developing renal scarring, regardless of whether he/she has VUR. Our specific aims are (1) to compare the proportion of children who develop renal scarring 2 years from the index UTI among children in the ancillary study who do not have VUR and those in the RIVUR study who do have VUR and are receiving placebo, and (2) to develop a prediction rule that accurately identifies a group of children at high risk of developing renal scarring as well as a group of children with virtually no risk of developing renal scarring after the index UTI.PROJECT NARRATIVE Understanding which children are at the greatest risk of renal scarring after a UTI will allow clinicians to provide more targeted therapies and interventions to prevent this adverse outcome.